The "Gerbil Food Cocktail"

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"Give with a free hand, but give only your own."
-- J.R.R. Tolkien The Children of Hurin
- The "Gerbil Food Cocktail" -

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Observations:

The "Gerbil Food Cocktail"

+ Choline [how much? From eggs, lecithin, or as a supplement]
+ Uridine monophosphate [how much or from what alternative source? Uridine triphosphate? Brewer's yeast? Orotates?]
+ DHA [How much? From fish oil]

[Without having any further guidance on how much of each and how often, and until we have more information, all we can do is go by supplement manufacturer's recommended dosages.]

DHA: Fish oil

Choline: Choline or "citi-choline" supplements, lecithin.

Uridine: Sugar beets, molasses (from sugar beets), tomatoes (0.5 to 1.0 g uridine per kilogram dry weight), brewer’s yeast (3% uridine by dry weight)[3], beer (from the yeast), broccoli, "orotates", organ meats (liver, pancreas, etc.).

I'm going to use fish oil, lecithin, and brewer's yeast for myself. I will use the recommended dose on the label.

Interestingly, for anyone battling depression, I found lots of articles from about 2006 saying that a combination of DHA (fish oil) and uridine was about as effective as Prozac.

Get Smart About What You Eat And You Might Actually Improve Your Intelligence

ScienceDaily (July 3, 2008)
New research findings published online in The FASEB Journal provide more evidence that if we get smart about what we eat, our intelligence can improve. According to MIT scientists, dietary nutrients found in a wide range of foods from infant formula to eggs increase brain synapses and improve cognitive abilities... In the study, gerbils were given various combinations of three compounds needed for healthy brain membranes: choline, found in eggs; uridine monophosphate (UMP) found in beets; and docosahexaenoic acid (DHA), found in fish oils. Other gerbils were given none of these to serve as a baseline. Then they were checked for cognitive changes four weeks later.
http://www.sciencedaily.com/releases/2008/07/080702150706.htm

Cocktail Therapy For Alzheimer's Disease? Works for Gerbils

ScienceDaily (July 9, 2008) — A dietary cocktail that includes a type of omega-3 fatty acid can improve memory and learning in gerbils, according to the latest study from MIT researchers that points to a possible beverage-based treatment for Alzheimer's and other brain diseases... The cocktail has previously been shown to promote growth of new brain connections in rodents.

"It may be possible to use this treatment to partially restore brain function in people with diseases that decrease the number of brain neurons, including, for example, Alzheimer's disease, Parkinson's, strokes and brain injuries."

The researchers found that normal gerbils treated with the mixture--a combination of DHA (a type of omega-3 fatty acid), uridine and choline--performed significantly better on learning and memory tests than untreated gerbils...
http://www.sciencedaily.com/releases/2008/07/080708155604.htm

Dietary uridine enhances the improvement in learning and memory produced by administering DHA to gerbils.
Sarah Holguin, Joseph Martinez, Camille Chow, and Richard Wurtman. FASEB Journal, July 7, 2008 DOI: 10.1096/fj.08-112425
http://dx.doi.org/10.1096/fj.08-112425

MIT Research Offers New Hope For Alzheimer's Patients
ScienceDaily (Apr. 27, 2006) — CAMBRIDGE, Mass.--MIT brain researchers have developed a "cocktail" of dietary supplements, now in human clinical trials, that holds promise for the treatment of Alzheimer's disease... he three compounds in the treatment cocktail - omega-3 fatty acids, uridine and choline - are all needed by brain neurons to make phospholipids, the primary component of cell membranes... the new research focuses on brain synapses, where neurotransmitters such as dopamine, acetylcholine, serotonin and glutamate carry messages from presynaptic neurons to receptors in the membranes of postsynaptic neurons... the researchers detected a large increase in the levels of specific brain proteins known to be concentrated within synapses, indicating that more synaptic membranes had formed... Synaptic membrane protein levels rose if the gerbils were.. fed all three compounds... Choline can be found in meats, nuts and eggs, and omega-3 fatty acids are found in a variety of sources, including fish, eggs, flaxseed and meat from grass-fed animals. Uridine, which is found in RNA and produced by the liver and kidney, is not obtained from the diet. However, uridine is found in human breast milk, which is a good indication that supplementary uridine is safe for humans to consume, Wurtman said...
http://www.sciencedaily.com/releases/2006/04/060427215901.htm

Nutrition and Alzheimer's disease: pre-clinical concepts.
Kamphuis PJ, Wurtman RJ.
Danone Research-Centre for Specialised Nutrition, Wageningen, The Netherlands. patrick.kamphuis@danone.com
Abstract
Eur J Neurol. 2009 Sep;16 Suppl 1:12-8.
...An Alzheimer's brain contains fewer synapses and reduced levels of synaptic proteins and membrane phosphatides. Brain membrane phosphatide synthesis requires at least three dietary precursors: polyunsaturated fatty acids, uridine monophosphate (UMP) and choline. Animal studies have shown that administration of these nutrients increases the level of phosphatides, specific pre- or post-synaptic proteins and the number of dendritic spines - a requirement for new synapse formation. These effects are markedly enhanced when animals receive all three compounds together. This multi-nutrient approach in animals has also been shown to decrease amyloid beta protein (Abeta) plaque burden, improve learning and memory through increased cholinergic neurotransmission and have a neuroprotective effect in several mouse models of AD. Whether these potential therapeutic effects of a multi-nutrient approach observed in animal models can also be replicated in a clinical setting warrants further investigation.
PMID: 19703215 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/19703215

Use of phosphatide precursors to promote synaptogenesis.
Wurtman RJ, Cansev M, Sakamoto T, Ulus IH.
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. dick@mit.edu
Annu Rev Nutr. 2009;29:59-87.

Abstract

New brain synapses form when a postsynaptic structure, the dendritic spine, interacts with a presynaptic terminal. Brain synapses and dendritic spines, membrane-rich structures, are depleted in Alzheimer's disease, as are some circulating compounds needed for synthesizing phosphatides, the major constituents of synaptic membranes. Animals given three of these compounds, all nutrients-uridine, the omega-3 polyunsaturated fatty acid docosahexaenoic acid, and choline-develop increased levels of brain phosphatides and of proteins that are concentrated within synaptic membranes (e.g., PSD-95, synapsin-1), improved cognition, and enhanced neurotransmitter release. The nutrients work by increasing the substrate-saturation of low-affinity enzymes that synthesize the phosphatides. Moreover, uridine and its nucleotide metabolites activate brain P2Y receptors, which control neuronal differentiation and synaptic protein synthesis. A preparation containing these compounds is being tested for treating Alzheimer's disease.
PMID: 19400698 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/19400698

Synapse formation is enhanced by oral administration of uridine and DHA, the circulating precursors of brain phosphatides.
Wurtman RJ, Cansev M, Ulus IH.
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
J Nutr Health Aging. 2009 Mar;13(3):189-97.

Abstract

OBJECTIVE: The loss of cortical and hippocampal synapses is a universal hallmark of Alzheimer's disease, and probably underlies its effects on cognition. Synapses are formed from the interaction of neurites projecting from "presynaptic" neurons with dendritic spines projecting from "postsynaptic" neurons. Both of these structures are vulnerable to the toxic effects of nearby amyloid plaques, and their loss contributes to the decreased number of synapses that characterize the disease. A treatment that increased the formation of neurites and dendritic spines might reverse this loss, thereby increasing the number of synapses and slowing the decline in cognition. DESIGN SETTING, PARTICIPANTS, INTERVENTION,

MEASUREMENTS AND RESULTS: We observe that giving normal rodents uridine and the omega-3 fatty acid docosahexaenoic acid (DHA) orally can enhance dendritic spine levels (3), and cognitive functions (32). Moreover this treatment also increases levels of biochemical markers for neurites (i.e., neurofilament-M and neurofilament-70) (2) in vivo, and uridine alone increases both these markers and the outgrowth of visible neurites by cultured PC-12 cells (9). A phase 2 clinical trial, performed in Europe, is described briefly.

DISCUSSION AND CONCLUSION: Uridine and DHA are circulating precursors for the phosphatides in synaptic membranes, and act in part by increasing the substrate-saturation of enzymes that synthesize phosphatidylcholine from CTP (formed from the uridine, via UTP) and from diacylglycerol species that contain DHA: the enzymes have poor affinities for these substrates, and thus are unsaturated with them, and only partially active, under basal conditions. The enhancement by uridine of neurite outgrowth is also mediated in part by UTP serving as a ligand for neuronal P2Y receptors. Moreover administration of uridine with DHA activates many brain genes, among them the gene for the m-1 metabotropic glutamate receptor [Cansev, et al, submitted]. This activation, in turn, increases brain levels of that gene's protein product and of such other synaptic proteins as PSD-95, synapsin-1, syntaxin-3 and F-actin, but not levels of non-synaptic brain proteins like beta-tubulin. Hence it is possible that giving uridine plus DHA triggers a neuronal program that, by accelerating phosphatide and synaptic protein synthesis, controls synaptogenesis. If administering this mix of phosphatide precursors also increases synaptic elements in brains of patients with Alzheimer 's disease, as it does in normal rodents, then this treatment may ameliorate some of the manifestations of the disease.

PMID: 19262950 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/19262950

Synapse Formation and Cognitive Brain Development: effect of docosahexaenoic (DHA) and other dietary constituents
R. J. Wurtman, Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, Cambridge MA, 02139, USA;
Corresponding Author: R. J. Wurtman, Address: MIT, 43 Vassar St., 46-5023, Cambridge MA, 02139
Metabolism. Author manuscript; available in PMC 2009 October 1.
Published in final edited form as:
Metabolism. 2008 October; 57(Suppl 2): S6–10.
doi: 10.1016/j.metabol.2008.07.007.

PMCID: PMC2578826
NIHMSID: NIHMS71939

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2578826/

Dietary uridine enhances the improvement in learning and memory produced by administering DHA to gerbils.
Holguin S, Martinez J, Chow C, Wurtman R.
Massachusetts Institute of Technology, 43 Vassar St., 46-5023, Cambridge, MA 02139, USA.
FASEB J. 2008 Nov;22(11):3938-46. Epub 2008 Jul 7.

Abstract

This study examined the effects on cognitive behaviors of giving normal adult gerbils three compounds, normally in the circulation, which interact to increase brain phosphatides, synaptic proteins, dendritic spines, and neurotransmitter release. Animals received supplemental uridine (as its monophosphate, UMP; 0.5%) and choline (0.1%) via the diet, and docosahexaenoic acid (DHA; 300 mg/kg/day) by gavage, for 4 wk, and then throughout the subsequent period of behavioral training and testing. As shown previously, giving all three compounds caused highly significant (P<0.001) increases in total brain phospholipids and in each major phosphatide; giving DHA or UMP (plus choline) produced smaller increases in some of the phosphatides. DHA plus choline improved performance on the four-arm radial maze, T-maze, and Y-maze tests; coadministering UMP further enhanced these increases. (Uridine probably acts by generating both CTP, which can be limiting in phosphatide synthesis, and UTP, which activates P2Y receptors coupled to neurite outgrowth and protein synthesis. All three compounds also act by enhancing the substrate-saturation of phosphatide-synthesizing enzymes.) These findings demonstrate that a treatment that increases synaptic membrane content can enhance cognitive functions in normal animals.

PMID: 18606862 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/18606862
Full text (free): http://www.fasebj.org/cgi/reprint/22/11/3938

Chronic administration of DHA and UMP improves the impaired memory of environmentally impoverished rats.
Holguin S, Huang Y, Liu J, Wurtman R.
Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, 43 Vassar Street, 46-5023, Cambridge, MA 02139, USA.
Behav Brain Res. 2008 Aug 5;191(1):11-6. Epub 2008 Mar 18.

Abstract

Living in an enriched environment (EC) during development enhances memory function in adulthood; living in an impoverished environment (IC) impairs memory function. Compounds previously demonstrated to improve memory among IC rats include CDP-choline and uridine monophosphate (UMP). Brain phosphatidylcholine (PC) synthesis utilizes both the uridine formed from the metabolism of exogenous CDP-choline and UMP, and the choline formed from that of CDP-choline. It also uses the polyunsaturated fatty acid (PUFA) DHA, a precursor for the diacylglycerol incorporated into PC. DHA administration also improves cognition in young and aged rodents and humans; its effects on cognitively impaired IC rats have not been characterized. We have thus examined the consequences of administering DHA (300 mg/kg) by gavage, UMP (0.5% in the diet), or both compounds on hippocampal- and striatal-dependent forms of memory among rats exposed to EC or IC conditions for 1 month starting at weaning, and consuming a choline-containing diet. We observe that giving IC rats either dietary UMP or gavaged DHA improves performance on the hidden version of the Morris water maze (all P<0.05), a hippocampal-dependent task; co-administration of both phosphatide precursors further enhances the IC rats' performance on this task (P<0.001). Neither UMP nor DHA, nor giving both compounds, affects the performance of EC rats on the hidden version of the Morris water maze (P>0.05), nor the performance by IC or EC rats on the visible version of the Morris water maze (all P>0.05), a striatal-dependent task. We confirm that co-administration of UMP and DHA to rats increases brain levels of the phosphatides PC, PE, SM, PS, PI, and total brain phospholipid levels (all P<0.05), and show that rearing animals in an enriched environment also elevates brain PC, PS, and PI levels (all P<0.01) and total brain phospholipids (P<0.01) compared with their levels in animals reared in an IC environment. These findings suggest that giving DHA plus UMP can ameliorate memory deficits associated with rearing under impoverished conditions, and that this effect may be mediated in part through enhanced synthesis of brain membrane phosphatides.

PMID: 18423905 [PubMed - indexed for MEDLINE]PMCID: PMC2478743
http://www.ncbi.nlm.nih.gov/pubmed/18423905
Full text (free): http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2478743/?tool=pubmed

Nutrient 'Cocktail' Appears to Improve Dementia Symptoms

FRIDAY, Jan. 8, 2010 (HealthDay News) -- A combination of three nutrients might help improve memory in Alzheimer's patients by stimulating the growth of new brain connections (synapses), a new study shows.

Uridine, choline and the omega-3 fatty acid DHA (all found in breast milk) are precursors to the fatty molecules that make up brain cell membranes, which form synapses... In a clinical trial, 225 Alzheimer's patients were given a cocktail of the three nutrients, along with B vitamins, phosopholipids and antioxidants. Patients with mild Alzheimer's showed improvements in verbal memory...
http://news.yahoo.com/s/hsn/20100108/hl_hsn/nutrientcocktailappearstoimprovedementiasymptoms

Could Drink, Souvenaid, Be A Cure For Alzheimer's?
Study Will Determine Whether Nutrient-Laden Souvenaid Can Head Off Memory Loss

CHICAGO (CBS) Jan 11, 2010 8:45 pm US/Eastern
... It looks like a simple juice box, but inside there's a mixture called Souvenaid that could help Alzheimer's patients head off memory loss and possibly even improve their memory... "Souvenaid" contains vitamins and nutrients, including Uridine, fish oil components and Choline...
http://cbs4.com/health/Souvenaid.Alzheimers.drink.2.1419881.html

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